Displaying publications 201 - 220 of 888 in total

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  1. Suwanprinya L, Morales NP, Sanvarinda P, Dieng H, Okabayashi T, Morales Vargas RE
    Jpn J Infect Dis, 2017 07 24;70(4):383-387.
    PMID: 28003593 DOI: 10.7883/yoken.JJID.2016.236
    Encephalitis has been described worldwide as a severe complication in patients infected by dengue virus. Reactive oxygen species (ROS) production is a key mechanism involved in the neuronal damage caused by viral encephalitis. In the present study, the capability of dengue virus serotypes 2 (DENV2) and DENV4 to induce ROS production was investigated in a rat microglial cell line, HAPI cells. The cells were infected with DENV2 and DENV4 at a multiplicity of infection of 0.1 for a 2-h adsorption period. Japanese encephalitis virus (JEV) was used as the reference. DENV2- and DENV4-induced microglial activation and significantly increased ROS production corresponded to decreased cell viability. The activity of DENV4 was significantly higher than the activities of DENV2 and JEV at 48 and 72 h post infection. DENV4 partly induced ROS production via an iron-induced Fenton reaction, as demonstrated by the treatment with an iron chelator, deferiprone. Despite the induction of increased inducible nitric oxide synthase expression and nitric oxide (NO) production by JEV, DENV2, and DENV4 did not induce NO production, suggesting the activation of different pathways in response to infections by different viruses. In conclusion, DENV2 and DENV4 have the capability to induce ROS production and activate microglia, which have been reported as the key components of neuronal damage.
    Matched MeSH terms: Cell Survival/drug effects
  2. Hematpoor A, Paydar M, Liew SY, Sivasothy Y, Mohebali N, Looi CY, et al.
    Chem Biol Interact, 2018 Jan 05;279:210-218.
    PMID: 29174417 DOI: 10.1016/j.cbi.2017.11.014
    The aim of the present study is to isolate bioactive compounds from the roots of Piper sarmentosum and examine the mechanism of action using human breast cancer cell line (MDA-MB-231). Bioassay guided-fractionation of methanolic extract led to the isolation of asaricin (1) and isoasarone (2). Asaricin (1) and isoasarone (2) had significant cytotoxicity towards MDA-MB-231. MCF-10A (human normal breast epithelial cells) cells are less sensitive than MDA-MB-231, but they respond to the treatment with the same unit of measurement. Both compounds increase reactive oxygen species (ROS), decrease mitochondrial membrane potential (MMP) and enhance cytochrome c release in treated MDA-MB-231 cells. Isoasarone (2) markedly elevated caspase -8 and -3/7 activities and caused a decline in nuclear NF-κB translocation, suggesting extrinsic, death receptor-linked apoptosis pathway. Quantitative PCR results of MDA-MB-231 treated with asaricin (1) and isoasarone (2) showed altered expression of Bcl-2: Bax level. The inhibitory potency of these isolates may support the therapeutic uses of these compounds in breast cancer.
    Matched MeSH terms: Cell Survival/drug effects
  3. Abdul Manaf SA, Hegde G, Mandal UK, Wui TW, Roy P
    Curr Drug Deliv, 2017;14(8):1071-1077.
    PMID: 27745545 DOI: 10.2174/1567201813666161017130612
    BACKGROUND: Nano-scale carbon systems are emerging alternatives in drug delivery and bioimaging applications of which they gradually replace the quantum dots characterized by toxic heavy metal content in the latter application.

    OBJECTIVE: The work intended to use carbon nanospheres synthesized from biowaste Sago bark for cancer cell imaging applications.

    METHODS: This study synthesised carbon nanospheres from biowaste Sago bark using a catalyst-free pyrolysis technique. The nanospheres were functionalized with fluorescent dye coumarin-6 for cell imaging. Fluorescent nanosytems were characterized by field emission scanning electron microscopy-energy dispersive X ray, photon correlation spectroscopy and fourier transform infrared spectroscopy techniques.

    RESULTS: The average size of carbon nanospheres ranged between 30 and 40 nm with zeta potential of -26.8 ± 1.87 mV. The percentage viability of cancer cells on exposure to nanospheres varied from 91- 89 % for N2a cells and 90-85 % for A-375 cells respectively. Speedy uptake of the fluorescent nanospheres in both N2a and A-375 cells was observed within two hours of exposure.

    CONCLUSION: Novel fluorescent carbon nanosystem design following waste-to-wealth approach exhibited promising potential in cancer cell imaging applications.

    Matched MeSH terms: Cell Survival/drug effects
  4. Ganapathy R, Mani S, Hanumanth Rao BR, Tunku K, Ray B, Bhat A, et al.
    Front Biosci (Elite Ed), 2018 03 01;10:437-448.
    PMID: 29293467
    Thraatchathi Chooranam (TC), is a polyphenol-rich Indian traditional medicine. Present study was undertaken to investigate the effects of TC against H2O2 induced oxidative stress and apoptotic damage in H9C2 cardiomyocytes. Cell viability assay indicated relative safety (IC50= 488.10±12.04 mg/ml) of TC. Pretreatment of cells with TC upregulated anti-apoptotic Bcl2, and anti-oxidants TRX1 and TRXR and downregulated Bax and HIF-α and inflammatory genes iNOS and TNF-α. Together, these findings show that TC has both anti-oxidant and anti-apoptotic properties. Further studies may be considered to identify the bioactive principle(s) and precise mechanisms of action of TC.
    Matched MeSH terms: Cell Survival/drug effects
  5. Hasanpourghadi M, Majid NA, Mustafa MR
    Biochem Pharmacol, 2018 06;152:174-186.
    PMID: 29608909 DOI: 10.1016/j.bcp.2018.03.030
    We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC.
    Matched MeSH terms: Cell Survival/drug effects
  6. Zare-Zardini H, Taheri-Kafrani A, Amiri A, Bordbar AK
    Sci Rep, 2018 01 12;8(1):586.
    PMID: 29330486 DOI: 10.1038/s41598-017-18938-y
    In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2) and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell lines. The percentage of apoptotic cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The hemolysis and blood coagulation activity of nanostructures were performed. Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active against cancer cell lines in comparison with their cytotoxic activity against normal cell lines (MSCs) with IC50 values higher than 100 μg/ml. The results of TUNEL assay indicates a significant increase in the rates of TUNEL positive cells by increasing the concentrations of nanomaterials. Results were also shown that aggregation and changes of RBCs morphology were occurred in the presence of GO, GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had effect on blood coagulation system, especially on PTT. All nanostrucure act as antitumor drug so that binding of drugs to a nostructures is irresolvable and the whole structure enter to the cell as a drug.
    Matched MeSH terms: Cell Survival/drug effects
  7. MubarakAli D, LewisOscar F, Gopinath V, Alharbi NS, Alharbi SA, Thajuddin N
    Microb Pathog, 2018 Jan;114:323-327.
    PMID: 29229504 DOI: 10.1016/j.micpath.2017.11.043
    Chitosan is the second most abundant polymer obtained from the byproduct of seafood. Chitosan and its derivatives and chitosan loaded drugs are the recent area of interest against microbial pathogenesis. The cationic chitosan nanoparticles (ChNPs) interact with the anionic surfaces of the microbial cell membrane, which promotes antimicrobial activity. Although, ChNPs are potential against pathogenic microbes, selection of adaptable, suitable and cost effective synthesis method is much important. In the present study, ChNPs were synthesized adopting ionic gelation using sodium tripolyphosphate as a cross linking agent and characterized by FTIR, DLS, SEM and TEM analysis. ChNPs were investigated for antimicrobial activity against bacterial (Escherichia coli and Staphylococcus aureus) and fungal (Candida albicans) pathogens. ChNPs showed bactericidal activity at the lower minimum inhibitory concentration of about 40-80 μg mL-1. Interestingly, ChNPs exhibits biocompatible antioxidant property by inhibiting DPPH free radicals at 76% and also proven to be a potential candidate against the microbial pathogenesis with an inevitable applications in biomedicine.
    Matched MeSH terms: Cell Survival/drug effects
  8. Abu-Serie MM, Habashy NH, Attia WE
    BMC Complement Altern Med, 2018 May 10;18(1):154.
    PMID: 29747629 DOI: 10.1186/s12906-018-2218-5
    BACKGROUND: Since oxidative stress and inflammation are two linked factors in the pathogenesis of several human diseases. Thus identification of effective treatment is of great importance. Edible mushroom and microalgae are rich in the effective antioxidant phytochemicals. Hence, their beneficial effects on oxidative stress-associated inflammation are extremely required to be investigated.

    METHODS: This study evaluated the functional constituents, antioxidant and anti-inflammatory activities of Malaysian Ganoderma lucidum aqueous extract (GLE) and Egyptian Chlorella vulgaris ethanolic extract (CVE). Also, the synergistic, addictive or antagonistic activities of the combination between the two extracts (GLE-CVE) were studied. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-kappa B, as well as levels of nitric oxide, tumor necrosis factor (TNF)-α, lipid peroxidation, reduced glutathione and antioxidant enzymes were determined using in vitro model of lipopolysaccharide-stimulated white blood cells.

    Matched MeSH terms: Cell Survival/drug effects
  9. Alkhader E, Roberts CJ, Rosli R, Yuen KH, Seow EK, Lee YZ, et al.
    J Biomater Sci Polym Ed, 2018 12;29(18):2281-2298.
    PMID: 30376409 DOI: 10.1080/09205063.2018.1541500
    Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6 hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.
    Matched MeSH terms: Cell Survival/drug effects
  10. Ling YS, Lim LR, Yong YS, Tamin O, Puah PY
    Nat Prod Res, 2020 Jun;34(12):1796-1803.
    PMID: 30587039 DOI: 10.1080/14786419.2018.1531288
    Soft coral, Sinularia sp. had been proven to inherit promising anti-cancer properties against variety of cancer. Current study, Sinularia sp. extract was introduced to Hepatocellular carcinoma (Hep 3B). Cell viability assay indicated the extract exhibit a dose and time dependent cytotoxicity. LC50 exhibited the lowest at 72 h post treatment estimated as 45.3 µg/mL. Morphological alterations including nuclear condensation, cytoplasm shrinkage and deformed cellular shape in treated Hep 3B were observable. Chemometric analysis revealed hydrophobic metabolites were significantly altered. Elevated vitamin D and derivatives tend to up-regulation Ca2+ and ROS subsequently triggering apoptosis. Dysregulated glycerolipids may suggest that they were biotransformed to compensate the needs of phospholipids during cell damage. Perturbation of sphingolipids, ceramide and carbohydrate-conjugated ceramides species increased the release of pro-apoptotic components reside within mitochondria and promote programmed cell death in treated Hep 3B. To conclude, MS-based metabolomics enabled the characterization of Sinularia sp. extract-induced cell death.
    Matched MeSH terms: Cell Survival/drug effects
  11. Tan LT, Chan KG, Pusparajah P, Yin WF, Khan TM, Lee LH, et al.
    BMC Microbiol, 2019 02 13;19(1):38.
    PMID: 30760201 DOI: 10.1186/s12866-019-1409-7
    BACKGROUND: Colon cancer is the third most commonly diagnosed cancer worldwide, with a commensurately high mortality rate. The search for novel antioxidants and specific anticancer agents which may inhibit, delay or reverse the development of colon cancer is thus an area of great interest; Streptomyces bacteria have been demonstrated to be a source of such agents.

    RESULTS: The extract from Streptomyces sp. MUM265- a strain which was isolated and identified from Kuala Selangor mangrove forest, Selangor, Malaysia- was analyzed and found to exhibit antioxidant properties as demonstrated via metal-chelating ability as well as superoxide anion, DPPH and ABTS radical scavenging activities. This study also showed that MUM265 extract demonstrated cytotoxicity against colon cancer cells as evidenced by the reduced cell viability of Caco-2 cell line. Treatment with MUM265 extract induced depolarization of mitochondrial membrane potential and accumulation of subG1 cells in cell cycle analysis, suggesting that MUM265 exerted apoptosis-inducing effects on Caco-2 cells.

    CONCLUSION: These findings indicate that mangrove derived Streptomyces sp. MUM265 represents a valuable bioresource of bioactive compounds for the future development of chemopreventive agents, with particular promise suggested for treatment of colon cancer.

    Matched MeSH terms: Cell Survival/drug effects*
  12. Zarkasi KA, Jen-Kit T, Jubri Z
    Mini Rev Med Chem, 2019;19(17):1407-1426.
    PMID: 30706809 DOI: 10.2174/1389557519666190130164334
    Myocardial infarction is a major cause of deaths globally. Modulation of several molecular mechanisms occurs during the initial stages of myocardial ischemia prior to permanent cardiac tissue damage, which involves both pathogenic as well as survival pathways in the cardiomyocyte. Currently, there is increasing evidence regarding the cardioprotective role of vitamin E in alleviating the disease. This fat-soluble vitamin does not only act as a powerful antioxidant; but it also has the ability to regulate several intracellular signalling pathways including HIF-1, PPAR-γ, Nrf-2, and NF-κB that influence the expression of a number of genes and their protein products. Essentially, it inhibits the molecular progression of tissue damage and preserves myocardial tissue viability. This review aims to summarize the molecular understanding of the cardiomodulation in myocardial infarction as well as the mechanism of vitamin E protection.
    Matched MeSH terms: Cell Survival/drug effects
  13. Elendran S, Muniyandy S, Lee WW, Palanisamy UD
    Food Funct, 2019 Feb 20;10(2):602-615.
    PMID: 30566155 DOI: 10.1039/c8fo01927d
    Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.
    Matched MeSH terms: Cell Survival/drug effects
  14. Saleem H, Htar TT, Naidu R, Nawawi NS, Ahmad I, Ashraf M, et al.
    Food Chem Toxicol, 2019 Jan;123:363-373.
    PMID: 30419323 DOI: 10.1016/j.fct.2018.11.016
    We investigated into the effects of methanol and dichloromethane extracts from aerial and roots of Filago germanica (L.) Huds (Astearaceae) on key enzymes (cholinesterases, α-glucosidase and urease), antioxidant capabilities, cytotoxic potential and secondary metabolomics profile. Total phenolic and flavonoids were determined by spectrophotometric technique and secondary metabolites composition by UHPLC-MS. Antioxidant activities were assessed employing free radical scavenging, ferric reducing power and phosphomolybdenum assays. The cell-toxicity was evaluated by MTT assay against breast (MCF-7, MDA-MB-231), cervix (CaSki) and prostate (DU-145) cancers. Overall, methanol extracts were found to have higher total bioactive contents and antioxidant potential. UHPLC-MS analysis revealed significant variation in the secondary metabolites in the methanol extracts. The most common derivatives belong to seven groups i.e. alkaloids, benzoic acids, flavones, flavonols, flavan-3-ols, terpenoids and saponins. The major polyphenolic compounds were found to be kampferol, robinin, luteolin, ferulic acid, benzoic acid and salicylic acid. All the extracts showed moderate cholinesterases inhibition, whereas methanol extracts exhibited highest urease inhibition and all extracts presented a relatively high inhibition against α-glucosidase. Similarly, all extracts showed strong to moderate cytotoxicity with IC50 values ranging from 53.02 to 382.7 μg/mL. Overall, results have suggested F. germanica to be a lead source for novel natural products.
    Matched MeSH terms: Cell Survival/drug effects
  15. Ali MK, Moshikur RM, Wakabayashi R, Tahara Y, Moniruzzaman M, Kamiya N, et al.
    J Colloid Interface Sci, 2019 Sep 01;551:72-80.
    PMID: 31075635 DOI: 10.1016/j.jcis.2019.04.095
    Ionic liquid (IL) surfactants have attracted great interest as promising substitutes for conventional surfactants owing to their exceptional and favorable physico-chemical properties. However, most IL surfactants are not eco-friendly and form unstable micelles, even when using a high concentration of the surfactant. In this study, we prepared a series of halogen-free and biocompatible choline-fatty-acid-based ILs with different chain lengths and degrees of saturation, and we then investigated their micellar properties in aqueous solutions. Characterization of the synthesized surface-active ILs (SAILs) was performed by 1H and 13C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. The surface-active properties of the SAILs were investigated by tensiometry, conductometry, and dynamic light scattering measurements. The critical micelle concentration of the SAILs was found to be 2-4 times lower than those of conventional surfactants. The thermodynamic properties of micellization (ΔG0m, ΔH0m, and ΔS0m) indicate that the micellization process of the SAILs is spontaneous, stable, and entropy-driven at room temperature. The cytotoxicity of the SAILs was evaluated using mammalian cell line NIH 3T3. Importantly, [Cho][Ole] shows lower toxicity than the analogous ILs with conventional surfactants. These results clearly suggest that these environmentally friendly SAILs can be used as a potential alternative to conventional ILs for various purposes, including biological applications.
    Matched MeSH terms: Cell Survival/drug effects
  16. Ismail NI, Othman I, Abas F, H Lajis N, Naidu R
    Int J Mol Sci, 2019 May 17;20(10).
    PMID: 31108984 DOI: 10.3390/ijms20102454
    Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.
    Matched MeSH terms: Cell Survival/drug effects
  17. Xin J, Wan Mahtar WNA, Siah PC, Miswan N, Khoo BY
    Mol Med Rep, 2019 Jun;19(6):5368-5376.
    PMID: 31059050 DOI: 10.3892/mmr.2019.10201
    Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high‑throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H‑TOPOI) in a yeast‑based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H‑TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H‑TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H‑TOPOI. The findings of the current study indicated that SMD1168H‑TOPOI has similar characteristics to MDA‑MB‑231 cells; therefore, it can be used in a yeast‑based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.
    Matched MeSH terms: Cell Survival/drug effects
  18. Al-Ani LA, Yehye WA, Kadir FA, Hashim NM, AlSaadi MA, Julkapli NM, et al.
    PLoS One, 2019;14(5):e0216725.
    PMID: 31086406 DOI: 10.1371/journal.pone.0216725
    Nanotechnology-based antioxidants and therapeutic agents are believed to be the next generation tools to face the ever-increasing cancer mortality rates. Graphene stands as a preferred nano-therapeutic template, due to the advanced properties and cellular interaction mechanisms. Nevertheless, majority of graphene-based composites suffer from hindered development as efficient cancer therapeutics. Recent nano-toxicology reviews and recommendations emphasize on the preliminary synthetic stages as a crucial element in driving successful applications results. In this study, we present an integrated, green, one-pot hybridization of target-suited raw materials into curcumin-capped gold nanoparticle-conjugated reduced graphene oxide (CAG) nanocomposite, as a prominent anti-oxidant and anti-cancer agent. Distinct from previous studies, the beneficial attributes of curcumin are employed to their fullest extent, such that they perform dual roles of being a natural reducing agent and possessing antioxidant anti-cancer functional moiety. The proposed novel green synthesis approach secured an enhanced structure with dispersed homogenous AuNPs (15.62 ± 4.04 nm) anchored on reduced graphene oxide (rGO) sheets, as evidenced by transmission electron microscopy, surpassing other traditional chemical reductants. On the other hand, safe, non-toxic CAG elevates biological activity and supports biocompatibility. Free radical DPPH inhibition assay revealed CAG antioxidant potential with IC50 (324.1 ± 1.8%) value reduced by half compared to that of traditional citrate-rGO-AuNP nanocomposite (612.1 ± 10.1%), which confirms the amplified multi-potent antioxidant activity. Human colon cancer cell lines (HT-29 and SW-948) showed concentration- and time-dependent cytotoxicity for CAG, as determined by optical microscopy images and WST-8 assay, with relatively low IC50 values (~100 μg/ml), while preserving biocompatibility towards normal human colon (CCD-841) and liver cells (WRL-68), with high selectivity indices (≥ 2.0) at all tested time points. Collectively, our results demonstrate effective green synthesis of CAG nanocomposite, free of additional stabilizing agents, and its bioactivity as an antioxidant and selective anti-colon cancer agent.
    Matched MeSH terms: Cell Survival/drug effects
  19. Rothan HA, Abdulrahman AY, Khazali AS, Nor Rashid N, Chong TT, Yusof R
    J. Pept. Sci., 2019 Aug;25(8):e3196.
    PMID: 31290226 DOI: 10.1002/psc.3196
    Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted to humans by their common vector, Aedes mosquitoes. DENV infection represents one of the most widely spread mosquito-borne diseases whereas ZIKV infection occasionally re-emerged in the past causing outbreaks. Although there have been considerable advances in understanding the pathophysiology of these viruses, no effective vaccines or antiviral drugs are currently available. In this study, we evaluated the antiviral activity of carnosine, an endogenous dipeptide (β-alanyl-l-histidine), against DENV serotype 2 (DENV2) and ZIKV infection in human liver cells (Huh7). Computational studies were performed to predict the potential interactions between carnosine and viral proteins. Biochemical and cell-based assays were performed to validate the computational results. Mode-of-inhibition, plaque reduction, and immunostaining assays were performed to determine the antiviral activity of carnosine. Exogenous carnosine showed minimal cytotoxicity in Huh7 cells and rescued the viability of infected cells with EC50 values of 52.3 and 59.5 μM for DENV2 and ZIKV infection, respectively. Based on the mode-of-inhibition assays, carnosine inhibited DENV2 mainly by inhibiting viral genome replication and interfering with virus entry. Carnosine antiviral activity was verified with immunostaining assay where carnosine treatment diminished viral fluorescence signal. In conclusion, carnosine exhibited significant inhibitory effects against DENV2 and ZIKV replication in human liver cells and could be utilized as a lead peptide for the development of effective and safe antiviral agents against DENV and ZIKV.
    Matched MeSH terms: Cell Survival/drug effects
  20. Anwar A, Siddiqui R, Hameed A, Shah MR, Khan NA
    Med Chem, 2020;16(7):841-847.
    PMID: 31544702 DOI: 10.2174/1573406415666190722113412
    BACKGROUND: Acanthamoeba is an opportunistic pathogen widely spread in the environment. Acanthamoeba causes excruciating keratitis which can lead to blindness. The lack of effective drugs and its ability to form highly resistant cyst are one of the foremost limitations against successful prognosis. Current treatment involves mixture of drugs at high doses but still recurrence of infection can occur due to ineffectiveness of drugs against the cyst form. Pyridine and its natural and synthetic derivatives are potential chemotherapeutic agents due to their diverse biological activities.

    OBJECTIVE: To study the antiamoebic effects of four novel synthetic dihydropyridine (DHP) compounds against Acanthamoeba castellanii belonging to the T4 genotype. Furthermore, to evaluate their activity against amoeba-mediated host cells cytopathogenicity as well as their cytotoxicity against human cells.

    METHODS: Dihydropyridines were synthesized by cyclic dimerization of alkylidene malononitrile derivatives. Four analogues of functionally diverse DHPs were tested against Acanthamoeba castellanii by using amoebicidal, encystation and excystation assays. Moreover, Lactate dehydrogenase assays were carried out to study cytopathogenicity and cytotoxicity against human cells.

    RESULTS: These compounds showed significant amoebicidal and cysticidal effects at 50 μM concentration, whereas, two of the DHP derivatives also significantly reduced Acanthamoebamediated host cell cytotoxicity. Moreover, these DHPs were found to have low cytotoxicity against human cells suggesting a good safety profile.

    CONCLUSION: The results suggest that DHPs have potential against Acanthamoeba especially against the more resistant cyst stage and can be assessed further for drug development.

    Matched MeSH terms: Cell Survival/drug effects
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